Xcyte Therapies has developed a process ("Xcellerate") for the ex vivo activation and expansion of T cells using magnetic beads coated with antibodies to CD3 and CD28. Xcellerated T Cells from patients with CLL demonstrate an enhanced T cell repertoire, and the ability to induce the apoptosis of autologous tumor cells. Xcyte Therapies now plans to test this process as a therapy for patients with CLL. A dose escalation trial will be performed. The Specific Aims of this proposal are to: 1. Optimize large-scale bioreactor production of Xcellerated T Cells for CLL patients. Xcyte has developed a large-scale production process that will be able to achieve the cell doses required for the first two patient cohorts in the proposed clinical trial. Xcyte is now developing a bioreactor process to achieve the higher cell yields, which will be required to treat the third cohort of patients in the clinical trial. Xcyte will optimize and validate this process specifically for CLL. 2. Determine the safety & feasibility of infusinq Xcellerated T Cells in CLL patients in a dose escalation trial. Each patient will receive a single dose of Xcellerated T Cells. The cell dose will be escalated in cohorts of three patients each to determine the maximum tolerated dose (up to a maximum of 1 x 1011). The Xcellerated T Cell doses for each cohort will be: 1 x 1010, 3 x 1010, and 1 x 1011. Patients will be monitored carefully for toxicity. We will assess the influence of patient disease and prior treatment factors on final product characteristics. 3. Characterize immune reconstitution in patients treated with Xcellerated T Cells. We will assess changes in lymphocyte subsets by flow cytometry, immunoglobulin levels, and T cell repertoire by spectratyping. 4. Assess anti-tumor activity in CLL patients treated with Xcellerated T Cells. Patients will be monitored for clinical responses, changes in lymph node area, leukemic cell counts, expression of immunologic effector molecules on B cells, plasma cytokine levels, and anti-tumor T cell reactivity by ELISPOT. Xcyte Therapies has designed the clinical trial in collaboration with Dr. Thomas Kipps from the University of California, San Diego. He will serve as the principal clinical investigator for the trial. If the Xcellerate therapy can be determined to be safe, to improve the immune repertoire of patients, and to demonstrate evidence of anti-tumor activity, Xcyte will conduct subsequent trials to demonstrate its clinical benefit in CLL patients. Subsequent trials will also examine immune reconstitution following therapy with agents such as fludarabine and Campath